Abstract Leading health organizations around the world, both governmental and non-governmental, have recommended substantial reductions in consumption of simple sugars, in particular added sugars, to enhance human health. Unfortunately, due in large measure to the profound taste appeal of sweet foods and beverages, recommendations to reduce sugar intake have met with little or no success. An alternative approach to support a population-wide reduction in sugar consumption is to reduce added sugars in commercially available foods and beverages with the expectation that people would acclimate over time, such that reduced sugar products eventually become more palatable or even preferred. This approach arises from work on salt taste perception which has demonstrated that when people adopt an entire diet lower in sodium they gradually adjust over a two to three month period and actually come to prefer lower levels of saltiness. These findings formed the basis for an Institute of Medicine recommendation that the food industry gradually reduce salt in manufactured and restaurant food. The FDA and other governmental organizations worldwide support this approach to sodium reduction, and have taken steps to implement it. Would a similar approach work to decrease sugar intake? Unfortunately, very few controlled studies have assessed how sugar and sweetness in the diet affect perception and preference for sugar. Accordingly, we lack the data needed to convince government and industry stakeholders that people will acclimate to low sugar diets like they do to low salt diets. This project will determine whether such changes in sweet taste perception and preference follow reductions in dietary intake of added simple sugars. In this comprehensive clinical trial a USDA nutrition laboratory will supply all the foods and beverages that volunteers will consume over a period of three months. Healthy adults will be randomly assigned to one of four diet conditions. After a baseline month to establish normal sugar intake, Group 1 will receive a diet that is low in added simple sugars relative to the baseline month. For Group 2, sugar intake will be similarly reduced, but the reduction will occur gradually over the three-month diet manipulation. For Group 3, dietary sugar will be reduced as in Group 1, but sweetness exposure will be maintained using non-nutritive sweeteners. Group 4 (control) will not change intake of added simple. Data obtained will allow us to test the central hypothesis of this work: Reduction in sensory exposure to sugar alters sweet taste perception such that reduced sugar foods retain their palatability. Data supporting this hypothesis will in turn increase confidence that a strategy of population-wide sugar reduction will be tolerated by consumers and that it will accomplish a health-benefiting reduction in added simple sugar intake. Secondary outcomes of this work will address a potential sugar intake biomarker, effects of intake of sweeteners, primarily non-nutritive sweeteners, on the human gut microbiome, the hormonal effects of reduced sugar intake, as well as several other variables.